A phase II open-label study of cpi-613 in combination with modified (m)FOLFIRINOX in patients with locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4176-TPS4176
Author(s):  
David Lawrence Bajor ◽  
AMR MOHAMED ◽  
J. Eva Selfridge ◽  
Erin E. Anderson ◽  
Jeffrey Hardacre ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Open Label ◽  
Borderline Resectable ◽  
Nccn Guidelines

TPS4176 Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]

Phase II study evaluating trimodal therapy with cetuximab intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer [ISRCTN56652283]

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4100-4100 ◽  
Author(s):  
R. C. Krempien ◽  
M. W. Münter ◽  
C. Timke ◽  
P. E. Huber ◽  
H. Friess ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Locally Advanced Pancreatic Cancer ◽  
Trimodal Therapy ◽  
Tumor Bleeding

4100 Background: The induction of EGFR targeting with cetuximab in radiation based therapy of solid tumors has yielded promising results. Thus, we initiated a prospective Phase II trial designed to analyze the feasibility and effectivity of trimodal therapy with gemcitabine-based chemoradiation and cetuximab in locally advanced inoperable pancreatic cancer. Methods: In this phase 2 study, pts with locally advanced pancreatic cancer without prior cytotoxic therapy were treated with radiotherapy (RT), gemcitabine weekly (300 mg/m2), and cetuximab weekly (loading dose 400 mg/m2 day 1, and concomitant with radiation day 8,15,22,29,36 250 mg/m2). RT was delivered by using an integrated IMRT boost concept (54 Gy GTV, 45 Gy CTV) over 5 weeks. RT was followed by gemcitabine (1000 mg/m2) weekly × 3 in 4 weeks. Response evaluation using computed tomography followed at week 12. All amenable patients were intended for surgical treatment between week 12–15. Results: 24 pts were enrolled until now. Preliminary results are presented on 20 pts with the following characteristics: pancreatic adenocarcinoma c2 T4 N1 20/20, median age = 63.5 (range 51–79); M/F = 13/7; ECOG PS 0/1/2 = 2/12/6; median days on treatment: 90 (range 70–100). Treatment-related toxicities were observed in 16 pts. Grade 3 toxicities included diarrhea (n = 4), fatigue (n = 2), nausea (n = 3), neutropenia (n = 6), thrombocytopenia (n = 2), and vomiting (n = 2). 18/20 pts developed some acneiforme rush during therapy. No omittance of cetuximab therapy was necessary. 1 patient died during RT due to tumor bleeding. Median follow-up at present is 6 month, median survival has not been reached. Partial remissions 8/20, stable disease 9/20, progressive disease 3/20. 12/20 patients were amenable for secondary potentially curative resection. 4 patients could be resected, while 3 patients were found to have abdominal metastatic spread. Conclusions: Early data from trimodal therapy in pancreatic adenocarcinoma with chemoradiation (IMRT), gemcitabine, and cetuximab indicate feasibility without increased toxicity profile. The local response appears to be very promising in pancreatic cancer, potentially allowing neoadjuvant treatment. [Table: see text]

A phase II study of neoadjuvant gemcitabine/5-fluorouracil followed by 5-fluorouracil/oxaliplatin concurrent with radiation in patients with locally advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 259-259
Author(s):  
C. Lin ◽  
B. M. Kos ◽  
A. R. Sasson ◽  
J. L. Meza ◽  
J. L. Grem
Keyword(s):  
Pancreatic Cancer ◽  
Continuous Infusion ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Borderline Resectable ◽  
R1 Resection

259 Background: We designed this phase II trial to determine the efficacy and safety of a neoadjuvant regimen involving gemcitabine, infusional 5-fluorouracil (5-FU), oxaliplatin and radiation therapy (RT) in patients with locally advanced pancreatic adenocarcinoma Methods: Induction chemotherapy (CT) consisted of two 3-week cycles of weekly gemcitabine with 24-hour continuous infusion of 5 FU for 2 of 3 weeks. Chemoradiation (CRT) consisted of RT of 50.4 Gy in 28 fractions or 50 Gy in 25 fractions and weekly oxaliplatin with 24-hour continuous infusion of 5 FU throughout RT. The first 7 patients also received celecoxib 200 mg BID throughout induction CT and CRT. Upon completion of CRT, surgical candidates underwent a pancreatoduodenectomy. Response rate was assessed according to RECIST criteria 4 weeks after the end of CRT. CTC AE v3 was used to grade the acute side effects. The failure-free survival (FFS), overall survival (OS) and median survival were analyzed by the Kaplan Meier method. Results: Twenty-nine patients who had borderline resectable pancreatic adenocarcinoma at the UNMC were enrolled and received induction CT. Twenty-four patients completed CRT. Nineteen patients had surgical exploration: 4 were unresectable, 6 had intra-abdominal metastases, and 9 had resection (seven had R0 resection, 2 had R1 resection, and 6 had negative nodes). The median follow up was 27 months. There were maximum 48% acute grade 3-4 toxicities during induction CT and CRT. The median FFS and OS were 7 and 10 months and the 2-year FFS and OS were 17% and 28%. Median OS and FFS for patients with and without resection was 26 vs. 9 months, p=0.06; and 19 vs. 5 months, p=0.01. Patients with CA19-9 above 90 U/L throughout treatment had significantly shorter FFS and OS than patients with CA19-9 less than 90 throughout treatment or had a decline from baseline to less than 90 after treatment. Conclusions: Induction gemcitabine/5-FU followed by 5-FU/oxaliplatin concurrent with RT led to down staging in 31% patients with subsequent resection. Further innovative strategies are needed to improve the outcome of patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.

Decrease in CA-19-9 after neoadjuvant chemoradiation therapy to predict survival in locally advanced pancreatic cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 12-12
Author(s):  
Jaswinder Singh ◽  
Syed Faisal Jafri ◽  
Maninder Pabla ◽  
Bradley L. Freilich ◽  
Joe Cates ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Community Hospital ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Hospital Setting ◽  
Locally Advanced Pancreatic Cancer ◽  
Smoking History ◽  
Borderline Resectable

12 Background: Pancreatic adenocarcinoma is among the most lethal of human cancers. Data on overall survival rates of patients treated in the community hospital setting are limited. The purpose of this retrospective data collection study was to assess the CA19-9 change during the neo-adjuvant treatment of locally advanced pancreatic cancer patients and whether this test predicts the overall survival (OS). This study was conducted within a high volume community hospital setting. Methods: Eligibility included cytological or histological evidence of locally advanced, unresectable, and borderline resectable adenocarcinoma of the pancreas, not amenable for surgical resection. Resectability was determined with EUS and CT scan/MRI and was discussed in the multi-disciplinary conference. Patients diagnosed before July 2009 were treated with continuous 5-FU 200mg/m2 for 5 weeks with radiation of 1.8 Gy per daily fraction, for a total dose of 50.4 Gy over 5.5 weeks. Patients diagnosed after July 2009 received gemcitabine 400mg/m2 intravenously (over 60 minutes) beginning on the first day of radiation therapy (before radiation), then weekly thereafter during radiation. Results: Data were abstracted on 64 patients (40 deceased; 24 alive) diagnosed between 6/2005 and 4/2011. The median age was 68 years (range 41-87), and 52% were male. The majority of patients (97%) were diagnosed by endoscopic ultrasound (EUS) with biopsy. At diagnosis, 56 (88%) patients were locally advanced unresectable (without metastasis) or borderline resectable; 49 of these had neoadjuvant treatment, and 13 were later resected. Median OS for all 64 patients was 45.4 weeks (95% CI: 29.6-61.3), with no significant differences in OS by sex of patient (p = 0.210) or smoking history (p = 0.625). Twenty-two patients (34%) had >75% decreases in CA19-9 from baseline; median OS was 89.4 weeks in this group compared to 41.3 weeks in patients with changes in CA19-9 <75% (p = 0.025). Conclusions: This trial demonstrates improved overall survival in patients with locally advanced pancreatic cancer, who had significant decrease in CA19-9 (>75% decreases in CA19-9 from baseline) in response to neo-adjuvant chemotherapy and radiation.

Decrease in CA-19-9 after neoadjuvant chemoradiation therapy to predict survival in locally advanced pancreatic cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14632-e14632
Author(s):  
Jaswinder Singh ◽  
Syed Faisal Jafri ◽  
Maninder Pabla ◽  
Bradley L Freilich ◽  
Joe Cates ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Community Hospital ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Hospital Setting ◽  
Locally Advanced Pancreatic Cancer ◽  
Smoking History ◽  
Borderline Resectable

e14632 Background: Carcinoma of the pancreas is among the most lethal of human cancers. Data on the overall survival rates of patients treated in the community hospital setting are limited; the purpose of this retrospective data collection study was to assess – Does CA-19-9 change during the neo adjuvant treatment of locally advanced pancreatic cancer patients predicts the overall survival (OS) at high volume community hospital setting. Methods: Eligibility included cytological or histological evidence of locally advanced unresectable and borderline resectable adenocarcinoma of the pancreas, not amenable for complete surgical resection. Their respectability was determined with EUS and CT scan / MRI and was discussed in the multi disciplinary conference. Patients diagnosed before July 2009 were essentially treated with continuous 5-FU 200 mg/m2 for 5 weeks with radiation of 1.8 Gy per daily fraction, for a total dose of 50.4 Gy over 5.5 weeks. Patients diagnosed after July 2009 received gemcitabine 400 mg/m2 intravenously (over 60 minutes) beginning on the first day of radiation therapy (before radiation), then weekly thereafter during radiation. Results: Data were abstracted on 64 patients (40 deceased; 24 alive) diagnosed between 6/2005 and 4/2011. The median age was 68 years (range: 41-87), and 52% were male. The majority of patients (97%) were diagnosed by endoscopic ultrasound (EUS) with biopsy. At diagnosis, 56 (88%) patients were locally advanced unresectable(without metastasis) or borderline unresectable; 49 of these had neoadjuvant treatment, and 13 were later resected. Median OS for all 64 patients was 45.4 weeks (95% CI: 29.6-61.3), with no significant differences in OS by sex of patient (p = 0.210) or smoking history (p = 0.625). Twenty-two patients (34%) had >75% decreases in CA19-9 from baseline; median OS was 89.4 weeks in this group compared to 41.3 weeks in patients with changes in CA19-9 <75% (p = 0.025). Conclusions: This trial demonstrates improved overall survival in patients for patients with locally advanced pancreatic cancer , who had significant decrease in CA -19-9 (>75% decreases in CA19-9 from baseline) in response to neo adjuvant chemotherapy and radiation.

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